Iranian Journal of Kidney Diseases
Volume:9 Issue: 2, Mar 2015

Chronic kidney disease (CKD), especially when severe, is widely held as a contraindication to heart transplantation by many medical institutions. Given the widespread prevalence of CKD among heart transplant candidates, a nephrological assessment and management in potential heart transplant recipients is a key issue as renal impairment may potentially jeopardize the access of these patents to a life-saving procedure. Chronic heart and kidney diseases are intimately interconnected. First, both conditions share a great number of etiological factors. Second, a steady stream of studies have highlighted the negative heart-kidney interaction in such a way that any acute or chronic dysfunction of the former may affect the latter- and reciprocally-, as part of the «cardiorenal syndromes».

Immunologically, End Stage renal Disease (ESRD) is associated with some disorders in both innate and adaptive immune system in such a form that there is a coexistence of both immune activation and immune suppression. Although these disorders are complex yet thoroughly unknown, there is a close relation between the progressively defective immune system with side effects as well as mortality causes including cardiovascular problems, infections, and malignancies. From the other point, chronic inflammation as a major determinant of «dialysis syndrome» (including malnutrition, cachexia, and vasculopathy) is considered as the main factor of inability and mortality in dialysis patients. Such inflammation is generally arisen from immune system response to uremia and individual''s repetitive contact with dialysis instruments and, in the long term, leads to premature aging via intensifying tissue degeneration. Therefore, the immune system is known as one of the most important therapeutic targets to reduce morbidity and mortality in uremic and dialysis patients. This review addresses different aspects as well as mechanisms of immune system dysfunction and possible therapeutics in dialysis patients.

Vitamin E is a fat-soluble vitamin that functions as an antioxidant. The aim of this study was to investigate the effects of vitamins E supplementation in combination with antibiotics for the treatment of girls with acute pyelonephritis. This double-blinded randomized controlled trial was conducted on 152 girls aged 5 to 12 years with a first acute pyelonephritis episode based on technetium Tc 99m dimercaptosuccinic acid (99mTc-DMSA). They were randomized to receive a 14-day treatment with only antibiotics (control group; n = 76) and 14-day treatment with supplements of vitamin E (intervention group; n = 76) in addition to the antibiotics. Patient's clinical symptoms were monitored for 14 days and urine culture was performed 3 to 4 days and 7 to 10 days after the start of the treatment and its completion, respectively. All of the girls once underwent DMSA scan 4 to 6 months after the treatment. During the follow-up days, the mean frequency of fever (P =. 01), urinary frequency (P =. 001), urgency (P =. 003), dribbling (P =. 001), and urinary incontinence (P =. 006) were significantly lower in the intervention group compared to the control group. There was no significant difference in the results of urine culture 3 to 4 days after the start of treatment (P =. 16) and 7 to 10 days after its termination (P =. 37). There was also no significant difference between the results of DMSA scan 4 to 6 months after the start of treatment (P =. 31). Vitamin E supplementation has a significant effect in ameliorating sign and symptoms of UTI. However, further studies are recommended to confirm these findings.

Current assessment tools of autosomal dominant polycystic kidney disease (ADPKD) diagnosis are challenging. This study evaluated the possible application of assessment of interleukin (IL)-17-related cytokines and the circulatory T helper 17 cells in the diagnosis of ADPKD. Enrolling 54 ADPKD patients and 54 healthy individuals, we measured serum and urine levels of IL-6, IL-17, IL-23, and transforming growth factor-β and the peripheral blood frequency of T helper 17 cells through flowcytometry. We computed sensitivity and specificity of each inflammatory marker as well as their different combinations using the receiver operating characteristic curve and discriminant function analysis. The mean serum and urine levels of IL-17 and IL-23 as well as urine levels of IL-6 were higher in ADPKD patients compared to the healthy controls (P <. 001). There was no significant difference in the number of T helper 17 cells between the two groups. Among different combinations of the inflammatory markers, the serum IL-17 was the best factor in the diagnosis of ADPKD with a sensitivity as well as specificity of 100%. It is likely that T helper 17 pathway is involved in the pathogenesis of ADPKD; therefore, it may be beneficial if such a pathway be considered in its diagnosis.

Acute kidney injury (AKI) is a common complication of coronary artery bypass graft with several serious complications. This study aimed to find the incidence of AKI after coronary artery bypass graft and its complications based on the Acute Kidney Injury Network (AKIN) criteria. This study was done on 3470 patients who had undergone isolated coronary artery bypass graft. Acute kidney injury''s incidence was based on the AKIN criteria (only based on serum creatinine irrespective of urine output). Patients'' demographic data, in-hospital complications, and out-hospital mortality were collected from hospital databases and compared between the patients with and without AKI. Based on serum creatinine, the incidence of AKI was 27.7% (958 patients) on the 1st postoperative day. Nine patients (0.3%) needed hemodialysis during their hospital stay, and 31 patients (0.7%) developed persistent kidney failure until the discharge day. The number of patients undergoing hemodialysis was not significantly difference but persistent kidney failure was significantly more frequent in patients with AKI (P <. 001). Those with AKI also experienced longer length of stay (P =. 04) and longer length of stay in intensive care unit (P <. 001), and their mortality rate was higher in hospital (P <. 001) and during the 3-year follow-up period (P <. 001). Although AKI is associated with great patients'' morbidity and in-hospital and long-term mortality, most of AKI episodes after coronary artery bypass graft are mild with no need for hemodialysis, and they mostly improve spontaneously.

Nephronophthisis is of the most commonly inherited ciliopathies that leads to end-stage renal disease in children. The NPHP1 gene is the first identified gene responsible for nephronophthisis and related diseases. This study assessed mutations of the NPHP1 gene in 16 Iranian families with at least one member presenting features of nephronophthisis. Fifty-seven patients diagnosed with chronic kidney disease or end-stage renal disease were referred to Imam Hossein Children Hospital, in Isfahan, Iran. The gene analysis study was carried on 16 patients and their first-degree relatives (40 DNA samples) suspicious of having nephronophthisis. The NPHP1 deletion analysis was performed for exons 5, 7, and 20 of the NPHP1 gene. The patients'' median age was 15 years. The mean and median age of the first presentation was 10.06 ± 2.59 years and 10.5 years, respectively. A homozygous deletion was identified in the NPHP1 gene spanning at least from exon 5 to exon 20 in two families. High-throughput mutation analysis identified a homozygous truncating mutation (c.1504C>T, p.R502*) in the NPHP5 in 5 families. By combining NPHP1 deletion analysis with multiplex-polymerase-chain-reaction-based high-throughput mutation analysis we could identify the molecular disease-cause in 7 of 15 families from Iran. In 8 families, the molecular disease cause remained unknown.

Diabetic nephropathy is a major cause of morbidity and mortality among young adults with type 1 diabetes mellitus (DM). Albuminuria, the gold standard for early diagnosis, cannot always detect early diabetic nephropathy. We aimed at evaluating the level of urine neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubulointerstitial damage in children and adolescents with type 1 DM in relation to the level of albuminuria and other parameters. Fifty children with type 1 DM for more than 5 years were included in this study (mean age, 13. 8 ± 4. 0 years), and 18 healthy children served as controls. Patients with overt albuminuria (> 300 mg/g creatinine) or inflammatory states were excluded. Urine NGAL, microalbuminuria, and urine albumin-creatinine ratio were measured in patients and controls as well as other parameters. Urine NGAL was significantly higher in microalbuminuric in comparison with normoalbuminuric patients and controls, and correlated positively with urine albumin-creatinine ratio. A positive urine NGAL was observed in 12 of 38 normoalbuminuric patients (31. 6%) compared to 9 of 12 microalbuminuric patients (75%). A positive correlation was reported between urine NGAL and both Hemoglobin A1c and duration of DM, but not with estimated glomerular filtration rate or hypertension. Diabetic children, even some normoalbuminurics, showed increased urine NGAL. This finding may support the hypothesis of a «tubular phase» of diabetic disease preceding overt diabetic nephropathy, and hence, the use of urine NGAL measurement for early evaluation of renal involvement.

It has been suggested that a dialysate calcium concentration of 1.5 mmol/L is a compromise between bone protection and cardiovascular risk. This study aimed to investigate the effect of reducing dialysate calcium concentration to 1.5 mmol/L on mineral metabolism and hemodynamic parameters. Dialysate calcium concentration was changed from 1.75 mmol/L to 1.5 mmol/L for 9 months and observed the effects on mineral metabolism and dialysis outcome parameters in 52 hemodialysis patients. The results at 9 months demonstrated that postdialytic serum calcium level decreased significantly from 109 ± 7 mg/L to 102 ± 6 mg/L, intact parathyroid hormone (PTH) increased from 372 ± 52 pg/mL to 606 ± 80 pg/mL, and the oral alfacalcidol increased from 1.4 ± 0.3 µg/w to 3.3 ± 0.4 µg/w. In patients with low PTH levels, continuous increase of PTH was observed. There were no significant variation in the oral calcium carbonate dose and serum levels of alkaline phosphatase, predialytic calcium, and pre- and postdialytic phosphorus. The ultrafiltration rate and postdialysis systolic blood pressure were significantly lower after reducing the dialysate calcium concentration to 1.5 mmol/L. Intradialytic hypotension and cramps were more frequent with this dialysate calcium concentration. These findings demonstrated that a decrease in dialysate calcium concentration from 1.75 mmol/L to 1.5 mmol/L improved mineral metabolism by prevention of postdialytic hypercalcemia and releasing oversuppression of PTH, but it was associated with more use of oral alfacalcidol and more hemodynamic impairment.

The genetic variations of co-stimulatory molecules can affect the extent of T cell activity during T-cell mediated immunity, especially in transplant patients. This study aimed to investigate the association of programmed cell death 1 (PDCD1) and programmed cell death 1 ligand 1 (PDCD1LG1) gene polymorphisms with clinical outcome of kidney transplantation. A total of 122 patients with a kidney transplant were included in this retrospective study. Patients were classified into two groups of biopsy-proven acute allograft rejection (AAR) and stable graft function (SGF) during the 5-year follow-up period. Four single nucleotide polymorphisms in PDCD1 and PDCD1LG1 were determined in the groups of patients as well as in 208 healthy control individuals. The frequencies of PD-1.3 (+7146 G>A), PD-1.9 (+7625 C>T), PD-L1 (8923 A>C), and PD-L1 (+6777 C>G) genotypes and alleles were not significantly different between the AAR and SGF groups. In comparison with healthy controls, PD-1.9 (+7625 C>T) genotype and T allele were significantly more frequent in all of the patients and in those with SGF. Overall, 27 of 122 kidney allograft recipients experienced delayed graft function, and a higher frequency of PD-1.9 (+7625 C>T) genotype and T allele was observed in this group versus those without delayed graft function. Similarly, a significant high frequency of this genotype was found among the AAR subgroup of patients with delayed graft function. Our results indicate that potentially functional genetic variation in PDCD1 can influence the outcome of kidney transplantation.

Soluble major histocompatibility complex class I chain-related antigen A (soluble MICA) has recently been considered as an inhibitory molecule which is shed from tumors and protects them against natural killers and some subgroups of T cells'' cytolysis. In transplantation, soluble MICA is also a foreign antigenic molecule that can induce allospecific responses. This study aimed to clarify its possible role in long-term kidney allograft outcome. Thirty patients with biopsy-proven chronic allograft dysfunction (CAD) were pair-matched with kidney allograft recipients with 30 stable graft function. Fifteen healthy individuals were enrolled as controls. Soluble MICA antigen and anti-HLA antibodies were measured in their serum. There was no significant difference between CAD patients, stable recipients, and healthy volunteers in frequency or titer of soluble MICA; however, soluble MICA-positive patients were more frequent in the stable group was than the CAD group (43.4% versus 33.3%). In addition, a high level of soluble MICA was accompanied by enhanced humoral responses. No significant difference was found in anti-HLA antibodies production between the CAD and stable groups. Our data suggest that soluble MICA, at least in a defined range, can protect the allograft against natural killers and T cell cytolysis; nonetheless, its excessive amounts might stimulate immune system to exert enhanced humoral response. In order to confirm the protective or detrimental role of soluble MICA in kidney transplantation, conducting larger studies is necessary.

Arteriovenous fistula (AVF) is the best permanent access for hemodialysis. Swelling and pain due to thrombosis and infection is common at fistula site. Angiosarcoma is one of rare but important differential diagnosis of these signs. We present a patient on CAPD with angiosarcoma at AVF.

After renal transplantation approximately forty percent of patients with Membranous Glomerolunephritis (MGN) had a recurrence, most commonly during the first year.We present two cases with recurrent MGN after kidney transplantation who successfully treated with Ritoximab.